Epilepsy refers to any of various disorders marked by disturbed electrical rhythms of the central nervous system and is typically manifested by convulsive attacks or seizures. The prevalence of epilepsy is between 3 and 6 per 1,000 of the population.
In the great majority of cases, the cause of the disease is unknown and the disease is referred to as "primary" or "idiopathic" epilepsy. When the cause is known the disease is referred to as "secondary" or "symptomatic" epilepsy. The treatment of the disease is approached essentially in the same manner for both primary and secondary epilepsy.
The therapeutic goal for treating epilepsy is to prevent seizures. If managed well with known antiepileptic drugs, approximately 75% of treated patients may have their seizures controlled or reduced in frequency. This means that there are no known drugs available to adequately treat 25% of the patients who have epilepsy. The need, therefore, exists for new antiepileptic agents.
Of the known antiepileptic drugs the major clinically useful drugs are phenytoin, phenobarbital, ethosuximide, and valproate. As stated above, these drugs are only effective on approximately 75% of epileptic patients additionally these drugs exhibit adverse side effects due to varying degrees of toxicity which exist for the drugs.
The present invention discloses that certain malonamides exhibit anticonvulsant activity. Anticonvulsant activity of these malonamides have been evidenced in tests on mice and rats. Comparative studies of anticonvulsant activity as well as toxicity, absorption characteristics and safety of malonamides as compared to four known prototype antiepileptic drugs, i.e., phenytoin, ethosuximide, phenobarbital, and valproate were performed using mice and rats as subjects. The results suggest that the malonamides have good antiepileptic potential in humans.